TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14994	45205;45206;45207	chr2:178621942;178621941;178621940	chr2:179486669;179486668;179486667
N2AB	13353	40282;40283;40284	chr2:178621942;178621941;178621940	chr2:179486669;179486668;179486667
N2A	12426	37501;37502;37503	chr2:178621942;178621941;178621940	chr2:179486669;179486668;179486667
N2B	5929	18010;18011;18012	chr2:178621942;178621941;178621940	chr2:179486669;179486668;179486667
Novex-1	6054	18385;18386;18387	chr2:178621942;178621941;178621940	chr2:179486669;179486668;179486667
Novex-2	6121	18586;18587;18588	chr2:178621942;178621941;178621940	chr2:179486669;179486668;179486667
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Ig-101
• Domain position: 53
• Structural Position: 134
• Q(SASA): 0.1949
• Predicted PPI site: N

Reported SAVs

SNV	RS	DUET	PolyPhen-2	Condel	Rhapsody	REVEL	MVP	Source	MAF	Disease	Zygosity	Site annotation	mCSM PPI	Predicted PPI site	Comments	AFR	AMR	AMS	ASJ	EAS	EUR	FIN	MDE	NFE	SAS	OTH
A/V	None	None	0.005	N	0.155	0.106	0.428169733428	gnomAD-4.0.0	2.05514E-06	None	None	None	None	N	None	0	0	None	0	2.53704E-05	None	0	0	1.80031E-06	0	0

Saturation Mutagenesis

SAV	AlphaMissense (IC)	AlphaMissense Class (IC)	AlphaMissense (N2AB)	AlphaMissense Class (N2AB)	mCSM	mCSM class	PolyPhen-2	PolyPhen-2 Class	Rhapsody	Rhapsody Class	Condel	Condel Score	Site annotation	mCSM PPI	Predicted PPI site
A/C	0.5777	likely_pathogenic	0.5506	ambiguous	-1.106	Destabilizing	0.998	D	0.503	neutral	None	None	None	None	N
A/D	0.2851	likely_benign	0.2897	benign	-1.185	Destabilizing	0.974	D	0.601	neutral	None	None	None	None	N
A/E	0.2724	likely_benign	0.2789	benign	-1.269	Destabilizing	0.801	D	0.471	neutral	N	0.489972261	None	None	N
A/F	0.3474	ambiguous	0.3372	benign	-1.201	Destabilizing	0.949	D	0.628	neutral	None	None	None	None	N
A/G	0.1533	likely_benign	0.1567	benign	-1.076	Destabilizing	0.891	D	0.441	neutral	N	0.448701922	None	None	N
A/H	0.4524	ambiguous	0.4703	ambiguous	-1.014	Destabilizing	0.998	D	0.62	neutral	None	None	None	None	N
A/I	0.2563	likely_benign	0.2635	benign	-0.617	Destabilizing	0.728	D	0.442	neutral	None	None	None	None	N
A/K	0.3372	likely_benign	0.3642	ambiguous	-1.058	Destabilizing	0.728	D	0.457	neutral	None	None	None	None	N
A/L	0.196	likely_benign	0.1962	benign	-0.617	Destabilizing	0.525	D	0.445	neutral	None	None	None	None	N
A/M	0.2216	likely_benign	0.2428	benign	-0.542	Destabilizing	0.974	D	0.54	neutral	None	None	None	None	N
A/N	0.19	likely_benign	0.2	benign	-0.812	Destabilizing	0.974	D	0.611	neutral	None	None	None	None	N
A/P	0.1893	likely_benign	0.1938	benign	-0.676	Destabilizing	0.989	D	0.53	neutral	N	0.47922552	None	None	N
A/Q	0.2914	likely_benign	0.3189	benign	-1.097	Destabilizing	0.949	D	0.532	neutral	None	None	None	None	N
A/R	0.2728	likely_benign	0.2797	benign	-0.6	Destabilizing	0.016	N	0.255	neutral	None	None	None	None	N
A/S	0.09	likely_benign	0.0954	benign	-1.133	Destabilizing	0.891	D	0.476	neutral	N	0.480023346	None	None	N
A/T	0.0899	likely_benign	0.0926	benign	-1.138	Destabilizing	0.801	D	0.435	neutral	N	0.419126719	None	None	N
A/V	0.144	likely_benign	0.1414	benign	-0.676	Destabilizing	0.005	N	0.155	neutral	N	0.439444713	None	None	N
A/W	0.7213	likely_pathogenic	0.7235	pathogenic	-1.369	Destabilizing	0.998	D	0.692	prob.neutral	None	None	None	None	N
A/Y	0.5079	ambiguous	0.511	ambiguous	-1.017	Destabilizing	0.974	D	0.628	neutral	None	None	None	None	N

Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.